Ying Qing Chen

All Publications

• Semiparametric Trend Analysis for Stratified Recurrent Gap Times Under Weak Comparability Constraint STATISTICS IN BIOSCIENCES Liu, P., Huang, Y., Chan, K., Chen, Y. 2023

  View details for DOI 10.1007/s12561-023-09376-8

  View details for Web of Science ID 000999954100002

• Population-Level Effectiveness of an Inactivated Whole-Virion COVID-19 Vaccine: A Test Negative Case-Control Study in the Dominican Republic. Open forum infectious diseases Pérez-Then, E., Miric, M., Qian, H. Z., Chen, Y. Q., Wang, Y., Vallejo, V., Quezada, W., Flaquer, M., Olivo, J., Castillo, J., García, N., Calderón, K., Cueto, S., Veras, B., Russo, M., Jiménez, I., Guzmán, S., Garabito, L., Cueto, E., Colombo, F., Taveras, D., Torres, D., Baez, J., Yunen, J., Koenig, E., Pérez, E., López, O., Severino Medina, F. E., Wang, X., Shao, Y., Vermund, S. H. 2023; 10 (3): ofad075

  Abstract

  A continuing nationwide vaccination campaign began in the Dominican Republic on February 16, 2021 to prevent severe consequences of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Estimates of vaccine effectiveness under real-world conditions are needed to support policy decision making and inform further vaccine selection.We conducted a test-negative case-control study to assess the real-world effectiveness of nationwide coronavirus disease 2019 (COVID-19) vaccination program using an inactivated vaccine (CoronaVac) on preventing symptomatic SARS-CoV-2 infections and hospitalizations from August to November 2021 in the Dominican Republic. Participants were recruited from 10 hospitals in 5 provinces to estimate the effectiveness of full immunization (≥14 days after receipt of the second dose) and partial immunization (otherwise with at least 1 dose ≥14 days after receipt of the first dose).Of 1078 adult participants seeking medical care for COVID-19-related symptoms, 395 (36.6%) had positive polymerase chain reaction (PCR) tests for SARS-CoV-2; 142 (13.2%) were hospitalized during 15 days of follow up, including 91 (23%) among 395 PCR-positive and 51 (7.5%) among 683 PCR-negative participants. Full vaccination was associated with 31% lower odds of symptomatic infection (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.93) and partial vaccination was associated with 49% lower odds (OR, 0.51; CI, 0.30-0.86). Among 395 PCR-positive participants, full vaccination reduced the odds of COVID-19-related hospitalization by 85% (OR, 0.15; 95% CI, 0.08-0.25) and partial vaccination reduced it by 75% (OR, 0.25; 95% CI, 0.08-0.80); full vaccination was associated with reduced use of assisted ventilation by 73% (OR, 0.27; 95% CI, 0.15-0.49).Given the ancestral and delta viral variants circulating during this study period, our results suggest that the inactivated COVID-19 vaccine offered moderate protection against symptomatic SARS-CoV-2 infections and high protection against COVID-19-related hospitalizations and assisted ventilation. This is reassuring given that, as of August 2022, an estimated 2.6 billion inactivated CoronaVac vaccine doses had been administered worldwide. This vaccine will become a basis for developing multivalent vaccine against the currently circulating omicron variant.

  View details for DOI 10.1093/ofid/ofad075

  View details for PubMedID 36998630

  View details for PubMedCentralID PMC10043129

• On a simple estimation of the proportional odds model under right truncation. Lifetime data analysis Liu, P., Chan, K. C., Chen, Y. Q. 2023

  Abstract

  Retrospective sampling can be useful in epidemiological research for its convenience to explore an etiological association. One particular retrospective sampling is that disease outcomes of the time-to-event type are collected subject to right truncation, along with other covariates of interest. For regression analysis of the right-truncated time-to-event data, the so-called proportional reverse-time hazards model has been proposed, but the interpretation of its regression parameters tends to be cumbersome, which has greatly hampered its application in practice. In this paper, we instead consider the proportional odds model, an appealing alternative to the popular proportional hazards model. Under the proportional odds model, there is an embedded relationship between the reverse-time hazard function and the usual hazard function. Building on this relationship, we provide a simple procedure to estimate the regression parameters in the proportional odds model for the right truncated data. Weighted estimations are also studied.

  View details for DOI 10.1007/s10985-022-09584-2

  View details for PubMedID 36602639

• Pregnancy rates and clinical outcomes among women living with HIV enrolled in HPTN 052 AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Zangeneh, S. Z., Wilson, E. A., Ahluwalia, S., Donnell, D. J., Chen, Y. Q., Grinsztejn, B., Melo, M. G., Godbole, S. V., Hosseinipour, M. C., Taha, T., Kumwenda, J., McCauley, M., Cohen, M. S., Nielsen-Saines, K. 2022: 1-9

  Abstract

  HPTN 052 was a multi-country clinical trial of cART for preventing heterosexual HIV-1 transmission. The study allowed participation of pregnant women and provided access to cART and contraceptives. We explored associations between pregnancy and clinical measures of HIV disease stage and progression. Of 869 women followed for 5.70 (SD = 1.62) years, 94.7% were married/cohabitating, 96% initiated cART, and 76.3% had >2 past pregnancies. Of 337 women who experienced pregnancy, 89.3% were from countries with lower contraceptive coverage, 56.1% first started cART with PI-based regimens and 57.6% were 25-34 years old. Mean cART duration and condom use were similar among pregnant and nonpregnant individuals. Adjusting for confounders, viral load suppression (VLS) was not (aHR(CI) = 0.82(0.61, 1.08)) and CD4 was slightly associated with decreased rates of first pregnancy over time (aHR(CI) = 0.9(0.84, 0.95)); baseline VLS was associated with increased (aRR(CI) = 2.48(1.71, 3.59)) and baseline CD4 was slightly associated with decreased number of pregnancies (aRR(CI) = 0.9(0.85,0.96)) over study duration. Partner seroconversion was univariably associated with higher rates of first pregnancy (HR(CI) = 2.02(1.32,3.07)). Despite a background of higher maternal morbidity and mortality rates, our findings suggest that becoming pregnant does not pose a threat to maternal health in women with HIV when there is access to medical care and antiretroviral treatment.

  View details for DOI 10.1080/09540121.2022.2141187

  View details for Web of Science ID 000899520400001

  View details for PubMedID 36524872

• Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305) AIDS AND BEHAVIOR Mayer, K. H., Yuhas, K., Amico, K., Wilkin, T., Landovitz, R. J., Richardson, P., Marzinke, M. A., Eshleman, S. H., Cottle, L. M., Marcus, C., Chege, W., Rinehart, A. R., Rooney, J. F., Andrew, P., Salata, R. A., Magnus, M., Farley, J. E., Liu, A. Y., Frank, I., Ho, K., Santana, J., Stekler, J. D., Chen, Y. Q., McCauley, M., Gulick, R. M. 2022

  Abstract

  HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ2 = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ2 = 9.36, p = 0.009 and χ2 = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.

  View details for DOI 10.1007/s10461-022-03736-z

  View details for Web of Science ID 000809325200006

  View details for PubMedID 35687192

• A surrogate measure for time-varying biomarkers in randomized clinical trials Mathematics Y, Z., F, X., Y, W., Y. Q., C. 2022; 10 (4): 584

  View details for DOI 10.3390/math10040584

• Uptake of antiretroviral treatment and viral suppression among men who have sex with men and transgender women in sub-Saharan Africa in an observational cohort study: HPTN 075 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Palumbo, P. J., Zhang, Y., Clarke, W., Breaud, A., Sivay, M., Cummings, V., Hamilton, E. L., Guo, X., Ogendo, A., Kayange, N., Panchia, R., Dominguez, K., Chen, Y. Q., Sandfort, T. M., Eshleman, S. H. 2021; 104: 465–70

  Abstract

  HPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period.Assessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays.Over 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs <400 copies/mL increased from 21.9% to 57.8%. The rate of ART failure (detection of drugs without viral suppression) was similar at screening and 12 months (12.0% and 11.1%, respectively) and was similar among MSM and TGW. Two participants developed HIV drug resistance during follow-up.Over 12 months, ARV drug use in the cohort more than doubled and viral suppression increased nearly threefold without a significant increase in ART failure or drug resistance. These results suggest that ART can be successfully scaled up for HIV prevention and treatment in this high-risk population.

  View details for DOI 10.1016/j.ijid.2020.12.085

  View details for Web of Science ID 000632937400024

  View details for PubMedID 33440260

  View details for PubMedCentralID PMC8091139

• Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Zhang, Y., Wymant, C., Laeyendecker, O., Grabowski, M. K., Hall, M., Hudelson, S., Piwowar-Manning, E., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., Hakim, J. G., Kumwenda, J., Mills, L. A., Santos, B. R., Grinsztejn, B., Pilotto, J. H., Chariyalertsak, S., Makhema, J., Chen, Y. Q., Cohen, M. S., Fraser, C., Eshleman, S. H. 2021; 72 (1): 30-37

  Abstract

  Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction.Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env).Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction.We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

  View details for DOI 10.1093/cid/ciz1247

  View details for PubMedID 31922537

  View details for PubMedCentralID PMC7823077

• Measuring Surrogacy in Clinical Research With an Application to Studying Surrogate Markers for HIV Treatment-as-Prevention STATISTICS IN BIOSCIENCES Zhuang, R., Chen, Y. 2020; 12 (3): 295–323

  Abstract

  In clinical research, validated surrogate markers are highly desirable in study design, monitoring, and analysis, as they do not only reduce the required sample size and follow-up duration, but also facilitate scientific discoveries. However, challenges exist to identify a reliable marker. One particular statistical challenge arises on how to measure and rank the surrogacy of potential markers quantitatively. We review the main statistical methods for evaluating surrogate markers. In addition, we suggest a new measure, the so-called "population surrogacy fraction of treatment effect," or simply the p-measure, in the setting of clinical trials. The p-measure carries an appealing population impact interpretation and supplements the existing statistical measures of surrogacy by providing "absolute" information. We apply the new measure along with other prominent measures to the HIV Prevention Trial Network 052 Study, a landmark trial for HIV/AIDS treatment-as-prevention.

  View details for DOI 10.1007/s12561-019-09244-4

  View details for Web of Science ID 000585702200004

  View details for PubMedID 33737982

  View details for PubMedCentralID PMC7962622

• Introduction to Special Issue on 'Statistical Methods for HIV/AIDS Research' STATISTICS IN BIOSCIENCES Chen, Y. 2020; 12 (3): 263–66

  View details for DOI 10.1007/s12561-020-09296-x

  View details for Web of Science ID 000579725100001

  View details for PubMedID 33101525

  View details for PubMedCentralID PMC7569197

• The feasibility of recruiting and retaining men who have sex with men and transgender women in a multinational prospective HIV prevention research cohort study in sub-Saharan Africa (HPTN 075) JOURNAL OF THE INTERNATIONAL AIDS SOCIETY Sandfort, T. M., Hamilton, E., Marais, A., Guo, X., Sugarman, J., Chen, Y. Q., Cummings, V., Dadabhai, S., Dominguez, K., Panchia, R., Schnabel, D., Zulu, F., Reynolds, D., Radebe, O., Mbeda, C., Kamba, D., Kanyemba, B., Ogendo, A., Stirratt, M., Chege, W., Lucas, J., Fawzy, M., McKinstry, L. A., Eshleman, S. H. 2020; 23: e25600

  Abstract

  Men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA) are profoundly affected by HIV with high HIV prevalence and incidence. This population also faces strong social stigma and legal barriers, potentially impeding participation in research. To date, few multi-country longitudinal HIV research studies with MSM/TGW have been conducted in SSA. Primary objective of the HIV Prevention Trials Network (HPTN) 075 study was to assess feasibility of recruiting and retaining a multinational prospective cohort of MSM/TGW in SSA for HIV prevention research.HPTN 075, conducted from 2015 to 2017, was designed to enroll 400 MSM/TGW at four sites in SSA (100 per site: Kisumu, Kenya; Blantyre, Malawi; Cape Town, South Africa; and Soweto, South Africa). The number of HIV-positive persons was capped at 20 per site; HIV-positive persons already in care were excluded from participation. The one-year study included five biobehavioural assessments. Community-based input and risk mitigation protocols were included in study design and conduct.Of 624 persons screened, 401 were enrolled. One in five participants was classified as transgender. Main reasons for ineligibility included: (a) being HIV positive after the cap was reached (29.6%); (b) not reporting anal intercourse with a man in the preceding three months (20.6%); and (c) being HIV positive and already in care (17.5%). Five (1.2%) participants died during the study (unrelated to study participation). 92.9% of the eligible participants (368/396) completed the final study visit and 86.1% participated in all visits. The main, overlapping reasons for early termination included being (a) unable to adhere to the visit schedule, predominantly because of relocation (46.4%), and (b) unable to contact the participant (32.1%). Participants reported strong motivation to participate and few participation barriers. Four participants reported social harms (loss of confidentiality and sexual harassment by study staff) that were successfully addressed.HPTN 075 successfully enrolled a multinational sample of MSM/TGW in SSA in a prospective HIV prevention research study with a high retention rate and few documented social harms. This supports the feasibility of conducting large-scale research trials in this population to address its urgent, unmet HIV prevention needs.

  View details for DOI 10.1002/jia2.25600

  View details for Web of Science ID 000576983100009

  View details for PubMedID 33000911

  View details for PubMedCentralID PMC7527761

• Persistence of oral pre-exposure prophylaxis (PrEP) among adolescent girls and young women initiating PrEP for HIV prevention in Kenya AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Tapsoba, J., Zangeneh, S. Z., Appelmans, E., Pasalar, S., Mori, K., Peng, L., Tao, J., Drain, P., Okomo, G., Bii, S., Mukabi, J., Zobrist, S., Brady, M., Obanda, R., Madiang, D., Cover, J., Duerr, A., Chen, Y., Obong'o, C. 2020: 1–9

  Abstract

  The Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) Initiative aims to reduce HIV infections among adolescent girls and young women (AGYW) in Africa. Oral pre-exposure prophylaxis (PrEP) is offered through DREAMS in Kenya to eligible AGYW in high burden counties including Kisumu and Homa Bay. This study examines PrEP persistence among AGYW in high burden community-based PrEP delivery settings. We evaluated PrEP persistence among AGYW in the DREAMS PrEP program in Kisumu and Homa Bay using survival analysis and programmatic PrEP refill data collected between March through December 2017. Among 1,259 AGYW who initiated PrEP during the study period, the median persistence time in the program was 56 days (95% CI: 49-58 days) and the proportion who persisted 3 months later was 37% (95% CI: 34-40%). Persistence varied by county (p < 0.001), age at PrEP initiation (p = 0.002), marital status (p = 0.008), transactional sex (p = 0.002), gender-based violence (GBV) experience (p = 0.009) and current school attendance (p = 0.001) at DREAMS enrollment. Persistence did not vary with orphan status, food insecurity, condom use, age at first sexual encounter or engagement in age-disparate sex at DREAMS enrollment. Targeted strategies are needed to improve AGYW retention in the PrEP program.

  View details for DOI 10.1080/09540121.2020.1822505

  View details for Web of Science ID 000571280600001

  View details for PubMedID 32951437

  View details for PubMedCentralID PMC7981281

• Trial designs for evaluating combination HIV prevention approaches HIV RESEARCH & CLINICAL PRACTICE Chen, Y., Peng, L., Wang, Y., Appelmans, E., Dasgupta, S., Fleming, T. R. 2020; 21 (2-3): 72–82

  Abstract

  Combination HIV prevention approaches that include both biomedical and non-biomedical interventions often hold greater promise to improve health outcomes and reduce the risk of HIV transmission.Evaluate the relative properties of four leading candidate trial designs - 'single-factor', 'multi-arm', 'all-in-one', and 'factorial' designs - for assessing individual and/or combination prevention intervention approaches.Monte-Carlo simulations are conducted, assuming a putative combination approach could choose its components from two candidate biomedical interventions, i.e. Treatment-as-Prevention (TasP) and Pre-exposure Prophylaxis (PrEP), and three candidate behavioral interventions, i.e. linkage-to-care, counseling, and use of condoms. Various scenarios for individual components' effect sizes, their possible interaction, and the sample size based on real clinical studies are considered.The all-in-one and factorial designs used to assess a combination approach and the multi-arm design used to assess multiple individual components are consistently more powerful than single-factor designs. The all-in-one design is powerful when the individual components are effective without negative interaction, while the factorial design is more consistently powerful across a broad array of settings.The multi-arm design is useful for evaluating single factor regimens, while the all-in-one and factorial designs are sensitive in assessing the overall efficacy when there is interest in combining individual component regimens anticipated to have complementary mechanisms. The factorial design is a preferred approach when assessing combination regimens due to its favorable power properties and since it is the only design providing direct insights about the contribution of individual components to the combination approach's overall efficacy and about potential interactions.

  View details for DOI 10.1080/25787489.2020.1798083

  View details for Web of Science ID 000555063900001

  View details for PubMedID 32698705

  View details for PubMedCentralID PMC7608072

• Healthcare-related stigma among men who have sex with men and transgender women in sub-Saharan Africa participating in HIV Prevention Trials Network (HPTN) 075 study AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Mbeda, C., Ogendo, A., Lando, R., Schnabel, D., Gust, D. A., Guo, X., Akelo, V., Dominguez, K., Panchia, R., Mbilizi, Y., Chen, Y., Chege, W., Sandfort, T., HPTN 075 Protocol Team 2020; 32 (8): 1052–60

  Abstract

  ABSTRACT The inability to access health services when needed is a critical barrier to HIV prevention, treatment and care among men who have sex with men (MSM) and transgender women (TGW). Using data collected in HPTN 075, we explored factors associated with any experienced healthcare-related stigma. HPTN 075 was a cohort study to assess the feasibility of recruiting and retaining MSM and TGW in clinical trials in sub-Saharan Africa. Of 401 MSM and TGW enrolled at four sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town, Soweto, South Africa) 397 contributed to the analysis (79.9% cis-gender and 20.1% TGW). Of these, (45.3%; 180/397) reported one or more of healthcare-related stigma experiences. Most frequently reported experiences included fear to seek healthcare services (36.3%) and avoiding seeking such services because of the discovery of MSM status (29.2%). Few men and TGW (2.5%) reported having been denied health services because of having sex with men. In multivariable analysis, more participants in Soweto [adjusted odds ratio (AOR) = 2.60] and fewer participants in Blantyre (AOR = 0.27) reported any healthcare-related stigma experiences, in comparison to participants in Kisumu. MSM and TGW that did not have a supportive gay community to rely on were more likely to report any healthcare-related stigma experiences (AOR = 1.46), whereas MSM and TGW who reported high social support and who never had engaged in transactional sex were less likely to report such experiences (AOR = 0.76 and AOR = 0.43, respectively). Our results suggest that encouraging support groups for MSM and TGW as well as training and sensitizing healthcare staff, and the general community, on MSM and TGW health issues and cultural competence may reduce stigma, improve access to healthcare, which could ultimately reduce HIV transmission.

  View details for DOI 10.1080/09540121.2020.1776824

  View details for Web of Science ID 000542822200001

  View details for PubMedID 32500722

  View details for PubMedCentralID PMC7368806

• On a Statistical Transmission Model in Analysis of the Early Phase of COVID-19 Outbreak STATISTICS IN BIOSCIENCES Zhu, Y., Chen, Y. 2021; 13 (1): 1–17

  Abstract

  Since December 2019, a disease caused by a novel strain of coronavirus (COVID-19) had infected many people and the cumulative confirmed cases have reached almost 180,000 as of 17, March 2020. The COVID-19 outbreak was believed to have emerged from a seafood market in Wuhan, a metropolis city of more than 11 million population in Hubei province, China. We introduced a statistical disease transmission model using case symptom onset data to estimate the transmissibility of the early-phase outbreak in China, and provided sensitivity analyses with various assumptions of disease natural history of the COVID-19. We fitted the transmission model to several publicly available sources of the outbreak data until 11, February 2020, and estimated lock down intervention efficacy of Wuhan city. The estimated R 0 was between 2.7 and 4.2 from plausible distribution assumptions of the incubation period and relative infectivity over the infectious period. 95% confidence interval of R 0 were also reported. Potential issues such as data quality concerns and comparison of different modelling approaches were discussed.

  View details for DOI 10.1007/s12561-020-09277-0

  View details for Web of Science ID 000523054500001

  View details for PubMedID 32292527

  View details for PubMedCentralID PMC7113380

• A regularized estimation approach for case-cohort periodic follow-up studies with an application to HIV vaccine trials BIOMETRICAL JOURNAL Zhao, H., Wu, Q., Gilbert, P. B., Chen, Y. Q., Sun, J. 2020; 62 (5): 1176–91

  Abstract

  This paper discusses regression analysis of the failure time data arising from case-cohort periodic follow-up studies, and one feature of such data, which makes their analysis much more difficult, is that they are usually interval-censored rather than right-censored. Although some methods have been developed for general failure time data, there does not seem to exist an established procedure for the situation considered here. To address the problem, we present a semiparametric regularized procedure and develop a simple algorithm for the implementation of the proposed method. In addition, unlike some existing procedures for similar situations, the proposed procedure is shown to have the oracle property, and an extensive simulation is conducted and it suggests that the presented approach seems to work well for practical situations. The method is applied to an HIV vaccine trial that motivated this study.

  View details for DOI 10.1002/bimj.201900180

  View details for Web of Science ID 000514617400001

  View details for PubMedID 32080888

  View details for PubMedCentralID PMC7768636

• Methods for generalized change-point models: with applications to human immunodeficiency virus surveillance and diabetes data STATISTICS IN MEDICINE Tapsoba, J., Wang, C., Zangeneh, S., Chen, Y. 2020; 39 (8): 1167–82

  Abstract

  In many epidemiological and biomedical studies, the association between a response variable and some covariates of interest may change at one or several thresholds of the covariates. Change-point models are suitable for investigating the relationship between the response and covariates in such situations. We present change-point models, with at least one unknown change-point occurring with respect to some covariates of a generalized linear model for independent or correlated data. We develop methods for the estimation of the model parameters and investigate their finite-sample performances in simulations. We apply the proposed methods to examine the trends in the reported estimates of the annual percentage of new human immunodeficiency virus (HIV) diagnoses linked to HIV-related medical care within 3 months after diagnosis using HIV surveillance data from the HIV prevention trial network 065 study. We also apply our methods to a dataset from the Pima Indian diabetes study to examine the effects of age and body mass index on the risk of being diagnosed with type 2 diabetes.

  View details for DOI 10.1002/sim.8469

  View details for Web of Science ID 000510844600001

  View details for PubMedID 31997385

  View details for PubMedCentralID PMC7260994

• Adjusted time-varying population attributable hazard in case-control studies STATISTICAL METHODS IN MEDICAL RESEARCH Zhao, W., Zheng, J., Chen, Y., Hsu, L. 2020; 29 (1): 243–57

  Abstract

  Population attributable fraction is a widely used measure for quantifying the disease burden associated with a modifiable exposure of interest at the population level. It has been extended to a time-varying measure, population attributable hazard function, to provide additional information on when and how the exposure's impact varies over time. However, like the classic population attributable fraction, the population attributable hazard is generally biased if confounders are present. In this article, we provide a natural definition of adjusted population attributable hazard to take into account the effects of confounders, and its alternative that is identifiable from case-control studies under the rare disease assumption. We propose a novel estimator, which combines the odds ratio estimator from logistic regression model, and the conditional density function estimator of the exposure and confounding variables distribution given the failure times of cases or the current times of controls from a kernel smoother. We show that the proposed estimators are consistent and asymptotically normal with variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimators perform well in finite sample sizes. Finally, we illustrate the method by an analysis of a case-control study of colorectal cancer. Supplementary materials for this article are available online.

  View details for DOI 10.1177/0962280219831725

  View details for Web of Science ID 000508982300017

  View details for PubMedID 30799773

  View details for PubMedCentralID PMC7261419

• On a Shape-Invariant Hazard Regression Model with application to an HIV Prevention Study of Mother-to-Child Transmission STATISTICS IN BIOSCIENCES Zheng, C., Chen, Y. 2020; 12 (3): 340–52

  Abstract

  In survival analysis, Cox model is widely used for most clinical trial data. Alternatives include the additive hazard model, the accelerated failure time (AFT) model and a more general transformation model. All these models assume that the effects for all covariates are on the same scale. However, it is possible that for different covariates, the effects are on different scales. In this paper, we propose a shape-invariant hazard regression model that allows us to estimate the multiplicative treatment effect with adjustment of covariates that have non-multiplicative effects. We propose moment-based inference procedures for the regression parameters. We also discuss the risk prediction and the goodness of fit test for our proposed model. Numerical studies show good finite sample performance of our proposed estimator. We applied our method to the HIVNET 012 study, a milestone trial of single-dose nevirapine in prevention of mother-to-child transmission of HIV. From the HIVNET 012 data analysis, single-dose nevirapine treatment is shown to improve 18-month infant survival significantly with appropriate adjustment of the maternal CD4 counts and the virus load.

  View details for DOI 10.1007/s12561-019-09260-4

  View details for Web of Science ID 000491530600002

  View details for PubMedID 33312265

  View details for PubMedCentralID PMC7730855